Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Dual opioid pain therapy

a technology of opioid pain and opioids, applied in the direction of biocide, drug composition, dispersed delivery, etc., can solve the problems of many undesirable side effects of the use of opioids, nausea and vomiting, dizziness, constipation, etc., and achieve the effects of reducing the number of side effects of opioid us

Inactive Publication Date: 2009-11-26
QRXPHARMA
View PDF9 Cites 24 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0012]The present invention provides pharmaceutical compositions comprising morphine and oxycodone, or pharmaceutically acceptable salts thereof, in preferred ratios that provide superior analgesia and fewer side effects when compared to doses of the individual components that provide analgesic efficacy.

Problems solved by technology

Unfortunately, the effects produced by morphine and similar opioid compounds are associated with many undesirable side effects, all mediated through activation of the mu and other opioid receptors, and make them amenable to abuse.
The undesirable side effects associated with the use of opioids include nausea and vomiting, drowsiness, dizziness, constipation, respiratory depression and bladder dysfunction.
Further a major associated risk is that repeated daily administrations of morphine or morphine-like opioids will eventually induce significant tolerance to the therapeutic effects of the drug, as well as initiating some degree of physical dependence.
Addiction with physical dependence can be difficult to treat due to the effects of withdrawal associated with dependence.
Another undesirable effect of opioid tolerance is that the higher opioid requirements of highly tolerant patients treated for pain increase the likelihood of unpleasant non-analgesic side effects due to greater circulating concentrations of opioids and potentially toxic opioid metabolites (Smith, M. T., Clin. Exp. Pharmacol. Physiol.
Furthermore, it has been found that co-administration to rats of sub-antinociceptive (also termed sub-analgesic) doses of oxycodone with morphine results in synergistic levels of antinociception (Ross et al., Pain 2000, 84, 421-428).
Administration of equipotent-doses of either opioid alone resulted in sedation of the rats.
Smith et al. disclose dosing regimens in terms of mg of therapeutic composition per kg of patient body weight over varying periods of time, but does not disclose a ratio of morphine and oxycodone that provide synergistic analgesia to human patients with reduction of opioid-related side effects.
However, both L-methadone and morphine displayed only additive effects with oxymorphone, oxycodone, fentanyl, alfentayl or meperidine.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0069]Comparison of a Product Containing Morphine and Oxycodone in the Ratio of 3 to 2, Morphine to Oxycodone by Weight vs. Morphine Alone (Study 1) and a Product Containing Morphine and Oxycodone in the Ratio of 1 to 2, Morphine to Oxycodone by Weight vs. Morphine Alone (Study 2) in the Treatment of Chronic Non-Cancer Pain

Study Design

[0070]Both Study 1 and Study 2 were Phase II clinical trials in patients with chronic moderate to severe, non-cancer pain. Both designs were similar, in that they were randomized, double-blind, crossover studies in an inpatient facility for up to a seven day period, for each arm. A standard comparison of each treatment was morphine in both studies. The primary objectives of these protocols were to compare pain relief and safety attributable to either of the two treatment groups. Efficacy was assessed using a Visual Analogue Scale (VAS) pain based on a patient self assessment.

Efficacy

[0071]Study 1 was conducted in 21 patients with chronic non-cancer pai...

example 2

Efficacy and Safety Study of Products Containing Morphine and Oxycodone in a Ratio of 3 to 2 (by Weight) in Acute Pain

Study Design

[0080]This double-blind, ascending cohort, parallel treatment study (Study 3) evaluated analgesia and safety measures in 5 groups of patients with moderate to severe pain (numerical pain rating scale score, range 0-10, study inclusion score of at least 4) following bunionectomy surgery, a procedure that involves manipulation of metatarsal foot bone. Once each of the 256 patients had sufficient pain following surgery, they were randomized to oxycodone / morphine or placebo and received dosing for up to the next 48 hrs. The dosing schedule was flexible in that the inventor wanted to determine what dosing intervals were preferred (and the amount of drug received) by patients as a function of unit dose strengths of products oxycodone and morphine in the ratio of 3 to 2. Dosages administered were 3 / 2 mg, 6 / 4 mg, 12 / 8 mg and 18 / 12 mg or 0 / 0 mg (placebo). Patients...

example 3

[0085]Comparison of a Product Containing Morphine and Oxycodone in the Ratio of 3 to 2 vs. Morphine vs. Oxycodone (Study 4) in the Treatment of Acute Pain

[0086]The purpose of Study 4 was to compare the efficacy and opioid related adverse events of products containing morphine and oxycodone in the ratio of 3 to 2 by weight with its individual components.

Design and Main Measures

[0087]Study 4 was a double-blind, randomized, multicenter, 48 hr treatment duration, bunionectomy study. The fixed dose treatment arms (q6h) were (i) products containing morphine and oxycodone as follows: 12 mg / 8 mg and 6 mg / 4 mg, and (ii) 4 products containing the components alone as follows: morphine 12 mg, morphine 6 mg, oxycodone 8 mg and oxycodone 4 mg. Pain reduction over a 24 hr period (SPID24: area under the curve of the changes in pain from baseline for the 24 hr period following the first dose of study medication) was prospectively defined as the primary endpoint. Also, in this trial ibuprofen rescue ...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
Weightaaaaaaaaaa
Weightaaaaaaaaaa
Massaaaaaaaaaa
Login to View More

Abstract

Provided are pharmaceutical compositions and methods for the alleviation of pain in a patient with optimal ratios of morphine and oxycodone that provide superior analgesic efficacy and lower incidence of adverse side effects compared to morphine and oxycodone alone. The pharmaceutical compositions comprise morphine and oxycodone, or pharmaceutically acceptable salts thereof, in ratios of about 3 to 2 to about 1 to 2, morphine to oxycodone by weight.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application No. 61 / 128,246 filed May 20, 2008, and U.S. Provisional Application No. 61 / 143,863, filed Jan. 12, 2009, both of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]This invention is directed to pharmaceutical compositions comprising optimal combinations of morphine and oxycodone that provide synergistic efficacy and lower incidence of undesired side effects for patients undergoing pain therapy. Methods of use comprising administering an effective amount and ratio of the opioid compounds to treat patients suffering from pain are also provided.BACKGROUND OF THE INVENTION[0003]Opioid compounds remain key agents for the treatment of a wide variety of acute and chronic pain. The World Health Organization has recommended morphine as the analgesic of choice for the treatment of severe cancer pain. Additionally, morphine and related opioids a...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
IPC IPC(8): A61K31/485A61P29/00
CPCA61K9/0095A61K31/485A61K2300/00A61P29/00
Inventor STERN, WARRENPACE, GARY W.IGLESIA, FELIX A. DE LASMITH, MAREERICHARDS, PATRICIA
Owner QRXPHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com